Pancreatic enzyme therapy for pancreatic exocrine insufficiency

Abstract

Pancreatic exocrine insufficiency with steatorrhea is a major consequence of pancreatic diseases (eg, chronic pancreatitis, cystic fibrosis, severe acute necrotizing pancreatitis, pancreatic cancer), extrapancreatic diseases such as celiac disease and Crohn's disease, and gastrointestinal and pancreatic surgical resection. Recognition of this entity is highly relevant to avoid malnutrition-related morbidity and mortality. Therapy for pancreatic exocrine insufficiency is based on the oral administration of pancreatic enzymes aiming at providing the duodenal lumen with sufficient active lipase at the time of gastric emptying of nutrients. Administration of enzymes in the form of enteric-coated minimicrospheres avoids acid-mediated lipase inactivation and ensures gastric emptying of enzymes in parallel with nutrients. Nevertheless, such factors as acidic intestinal pH and bacterial overgrowth may prevent normalization of fat digestion even in compliant patients. The present article critically reviews current therapeutic approaches to pancreatic exocrine insufficiency.

Italian consensus guidelines for chronic pancreatitis

“…Therefore, it was considered that further studies should be carried out to confirm the above mentioned study, and the recommendation grade was set lower than the level of evidence. The main clinical consequences of chronic pancreatitis are malnutrition and steatorrhea, both due to fat maldigestion [86]. Pancreatic enzyme supplementation improves fat absorption in patients with chronic pancreatitis and pancreatic exocrine insufficiency [87].…”

“…Pancreatic enzyme supplementation improves fat absorption in patients with chronic pancreatitis and pancreatic exocrine insufficiency [87]. Enzyme supplementation therapy is able to normalize nutritional parameters such as liposoluble vitamins, prealbumin, and ferritin in patients without overt steatorrhea [86,88]. Steatorrhea occurs late in chronic pancreatitis (after a median of 10 to 12 years since the onset of the disease in about 50% of patients) [88], and it may be much more common than expected on clinical grounds only [89].…”

“…The concomitant use of PPI is not indicated in patients with an adequate response to pancreatic enzyme supplementation therapy. However, patients with pancreatic insufficiency can have a severely impaired pancreatic bicarbonate secretion which may be insufficient to neutralize the acidity of the chyme in the duodenum [86,92]. This can impair the enzyme supplementation therapy, even when adequate or high enzyme doses are given.…”

“…The efficacy of pancreatic enzyme preparations depends on the enzyme activity released in the duodenum together with the chyme duodenal load. In pancreatic enzyme supplements, pancrelipase is formulated within pH-sensitive enteric-coated microspheres which mix with the meal in the stomach, protect their enzyme content from gastric acidity, and empty in the duodenum with the chime, where coating rapidly disintegrates at pH 5.5 to release enzymes from the microspheres [86,95]. Minimicrospheres of 1.0 to 1.2 mm in diameter have been shown to be emptied simultaneously with the meal and are associated with a 25% higher therapeutic efficacy compared to 1.8−2.0 mm microspheres [86,96].…”

“…Surgery can impair pancreatic function. Pancreatic exocrine insufficiency (PEI) develops in patients following pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy [86,103]. PEI is found in most patients after partial pancreatic resection as well as in patients with chronic pancreatitis [86,104].…”